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Avaliação in vitro dos efeitos leishmanicida e imunomoduladores contra Leishmania infantum de lectinas isoladas de algas marinhas do litoral cearense

Wed, 01 Jan 2025 00:00:00 GMT

Título: Avaliação in vitro dos efeitos leishmanicida e imunomoduladores contra Leishmania infantum de lectinas isoladas de algas marinhas do litoral cearense Autor(es): Mesquita, Amanda de Menezes Abstract: Leishmaniasis, an infectious parasitic disease caused by protozoa of the genus Leishmania, is transmitted through the bite of infected female sandflies and primarily affects the mononuclear phagocytic system. Among its forms, visceral leishmaniasis (VL) is the most severe due to its high lethality. In Brazil, the drugs used for VL treatment include pentavalent antimonials and amphotericin B, which are associated with high toxicity and the emergence of resistant strains. Therefore, the search for new therapeutic agents is of great importance. This study aimed to investigate the immunomodulatory and leishmanicidal effects in vitro of lectins extracted from the red marine alga Solieria filiformis (Kützing) P.W. Gabrielson and the green alga Caulerpa cupressoides var. lycopodium against Leishmania infantum. After extraction and isolation of the lectins, cytotoxicity was evaluated in J774 macrophages. Subsequently, the leishmanicidal effect against the amastigote form of the parasite was assessed (24 and 48 hours post-infection) using concentrations of 5, 10, 25, 50, and 100 µg/mL. To understand the leishmanicidal mechanism of action, levels of nitric oxide (NO) and the pro- and anti-inflammatory cytokines IL-4, IL-6, IL-10, IL-12, and TNF-α were measured. The study also investigated the leishmanicidal effect of Solieria filiformis and Caulerpa cupressoides on promastigote forms. These proteins demonstrated significant leishmanicidal activity, reducing promastigote survival at different concentrations. LSf showed greater efficacy, with a reduction of up to 75.60% at 48 hours, while LCc achieved 55.68%. Regarding the leishmanicidal effect of LSf and LCc on amastigote forms in macrophages infected with L. infantum, LSf reduced the parasitic load more effectively than the positive control (GLU) at 24 and 48 hours, particularly at 100 μg/mL. NO production increased with LSf, especially at higher concentrations, while LCc induced a less pronounced increase in NO. As for cytokines, LSf elevated IL-12 and TNF-α only at specific concentrations and time points, whereas LCc significantly increased IL-10, indicating an anti-inflammatory effect. Both proteins induced IL-6 production in infected macrophages, with a more pronounced effect at 50 and 100 μg/mL. The data from this study suggest a promising immunomodulatory effect of lectins from red and green marine algae on L. infantum-infected macrophages, although further studies are needed to better elucidate the mechanisms of action of these compounds against this parasite.. Tipo: Dissertação

Distribuição dos valores do antígeno prostático específico em pacientes com hiperplasia prostática benigna e câncer prostático e em indivíduos sadios

Tue, 01 Jan 2002 00:00:00 GMT

Título: Distribuição dos valores do antígeno prostático específico em pacientes com hiperplasia prostática benigna e câncer prostático e em indivíduos sadios Autor(es): Figueiredo, Maria de Fátima Abstract: Benign prostatic hyperplasia (BPH) and prostatic adenocarcinomas (PC) are among the most common pathologies of Brazilian adult men. The preliminary diagnostic criteria most used forthese pathologies include digital rectal examination (DRE), and measurement of serum prostate specific antigen (PSA). The aim of the present studies was to evaluate the distribution of total serum PSA leveis (PSA-st), in patients with confirmed diagnosis for prostate pathologies, and the influence of DRE on the PSA-st leveis in healthy adult men; as also the normal leveis of PSA-st in healthy adult males. Of the 147 patients studied, 85 (58.6%) had HPB, and 62 (41.4%) were diagnosed with PC. In the patients with HPB, the PSA-st values varied from 0.01 to 83.00 ng/mL; with a mean value of 9.43 ± 10.30 ng/mL, and a median value of 7.70 ng/mL. Sixteen of these patients (18.8%) revealed PSA-st leveis below 4.00 ng/mL; while in 22 (25,9%) the values were higher than 10.00 ng/mL; indicating that 44.7% of the patients diagnosed for HPB had PSA-st leveis outside the range considered suggestive of this pathology. The PSA-st leveis of 62 patients with prostatic câncer were generally higher than those for HPB; with the values ranging from 0.01 and 500 ng/mL, and median and mean values, respectively, of 13.40 and 38.90 ± 85.11 ng/mL. Twenty two (32.3%) of the cases of PC had PSA-st values below 10 ng/mL; while four (6.2%) revealed leveis between 129 and 500 ng/mL. The median values of the patients with HPB and PC were highly significantly different (p < 0.001). In both the pathologies, the PSA-st leveis increased with higher age; but the median values among the age groups were not statistically significant, either in individuais with HPB or in PC patients (p >0.05). DRE carried out in 48 healthy males, induced only modest, and non-significant, elevations in PSA-st leveis in a minority. A normal adult male population of 469 individuais revealed mean and median PSA-st values of 2.40 ± 4.30 ng/mL and 1.20 ng/mL; respectively; with the values increasing in higher age groups. The median values among the age groups were significantly different (p < 0.001). Our observations on the PSA-st values of patients with confirmed diagnosis suggest that the PSA-st values show a quantitative relation, in general, with each of the pathologies; without revealing distributions of values that enable a definite characterization of either HPB or PC. Tipo: Dissertação

Evolução e desfecho da leucemia mieloide crônica em mulheres grávidas: uma análise retrospectiva em um serviço de referência em hematologia

Thu, 01 Jan 2026 00:00:00 GMT

Título: Evolução e desfecho da leucemia mieloide crônica em mulheres grávidas: uma análise retrospectiva em um serviço de referência em hematologia Autor(es): Pereira, Bárbara Rebeca Alves Abstract: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome and the formation of the BCR-ABL1 fusion gene, which is responsible for constitutive tyrosine kinase activity and uncontrolled cellular proliferation. The introduction of tyrosine kinase inhibitors (TKIs) has transformed the prognosis of the disease, enabling deep and sustained hematologic, cytogenetic, and molecular responses.However, pregnancy during treatment requires temporary discontinuation of therapy, which may compromise the maintenance of response and disease control. The aim of this study was to evaluate the clinical course and outcomes of CML in women who became pregnant while receiving TKIs, followed at a hematology referral center in the state of Ceará, Brazil.This is an observational, descriptive, and retrospective study that included patients over 18 years of age with a clinical, cytogenetic, and/or molecular diagnosis of CML, receiving TKIs, who had a confirmed pregnancy between January 2002 and December 2024. Sociodemographic variables, prognostic scores, hematologic, cytogenetic, and molecular response profiles, therapeutic management during pregnancy, time to TKI reintroduction, and disease evolution after delivery were analyzed. Statistical analyses were performed using R software, with p < 0.05 considered significant.A total of 26 pregnancies were identified in 19 women with CML, among approximately 243 patients followed at the center. The mean age at diagnosis was 27 years, with a predominance of low-risk patients according to the prognostic scores evaluated. At the time of conception, 38% of pregnancies occurred in patients with major or deep molecular response, while 62% had not yet achieved an adequate molecular response.During pregnancy, there was a significant increase in the frequency of molecular response loss compared to the pre-pregnancy period (p < 0.05). TKI discontinuation was statistically associated with this loss (p < 0.05), particularly among patients who did not have a deep molecular response prior to conception.After TKI reintroduction in the postpartum period, a significant recovery of molecular response was observed (p < 0.05). Most patients regained at least a major molecular response, and some achieved deep molecular response again. A statistically significant association was observed between pre-pregnancy deep molecular response and a higher likelihood of response recovery after delivery, with a greater proportion of recovery in the previously responsive group (p < 0.05).There were two cases of disease progression and two deaths after pregnancy. Overall survival and event-free survival, estimated by Kaplan–Meier analysis, remained high throughout follow-up. Cases of therapeutic failure or need for permanent TKI switch were infrequent.Pregnancy outcomes were favorable, with a predominance of term births and no significant increase in severe complications. These findings indicate that, under appropriate monitoring, temporary discontinuation of therapy may lead to reversible molecular instability, reinforcing the importance of achieving a deep molecular response prior to conception for better hematologic outcomes. Tipo: Dissertação

Leishmania braziliensis resistente ao antimoniato de meglumina imunomodula a resposta de macrófagos murinos M1 e M2 in vitro

Thu, 01 Jan 2026 00:00:00 GMT

Título: Leishmania braziliensis resistente ao antimoniato de meglumina imunomodula a resposta de macrófagos murinos M1 e M2 in vitro Autor(es): Eugenio, Ana Lívia Rodrigues Abstract: Leishmania braziliensis is the main etiological agent of cutaneous leishmaniasis (CL), a disease with a high incidence in Brazil, representing a significant public health challenge. Meglumine antimoniate is the standard drug for treating the disease; however, the emergence of resistant strains has hampered its effectiveness. Macrophages act as host cells for Leishmania and play a fundamental role in the immune response against these parasites. The activation of macrophages to the M1 inflammatory profile is crucial for parasite elimination, but there is still little knowledge about how resistant strains of L. braziliensis modulate the plasticity of these cells. Therefore, the objective was to eva-luate the immunomodulation of murine macrophages in in vitro infection by L. brazi-liensis strains resistant (LbR) and susceptible (LbS) to meglumine antimoniate. To this end, murine J774 macrophages were polarized to M1 (with 1μg/ml of LPS) or M2 (with 1μg/ml of IL-4) and then infected with LbR or LbS strains. After 24 and 48h, the fol-lowing were analyzed: parasite load, cytokine production (TNF-α, IL-12, IL-6, IL-4 and IL-10), nitric oxide (NO), urea and arginase activity. The results demonstrated that M1 macrophages infected with LbR presented a significantly higher parasite load compared to those infected with LbS, in both periods evaluated. Regarding inflammatory media-tors, infection with LbR resulted in lower levels of TNF-α, IL-12, and NO in the group of M1 macrophages infected with the LbR strain, compared to M1 macrophages in-fected with the LbS strain. Conversely, in M2 macrophages, infection with LbR induced a significant production of IL-10, IL-4, and IL-6, while LbS did not provoke a relevant response in the production of these cytokines. Arginase and urea modulate the immune response by influencing macrophage polarization and the efficiency of the immune re-sponse to the parasite. These data suggest that the LbR strain has the ability to decrease the production of inflammatory cytokines and NO in M1 macrophages, as well as in-duce the production of regulatory cytokines in M2. This results in a less inflammatory intracellular environment, favoring the survival of the parasite and, consequently, its persistence, which hinders the treatment and cure of the disease. These findings high-light the need for further studies that can deepen the understanding of the resistance mechanisms of these protozoa to traditional therapies, which may contribute to the de-velopment of new, more effective therapeutic strategies. Tipo: Dissertação